2f2c: Difference between revisions

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[[Image:2f2c.gif|left|200px]]<br /><applet load="2f2c" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2f2c, resolution 2.80&Aring;" />
'''X-ray structure of human CDK6-Vcyclinwith the inhibitor aminopurvalanol'''<br />


==Overview==
==X-ray structure of human CDK6-Vcyclinwith the inhibitor aminopurvalanol==
Cyclin-dependent kinases (CDKs) are key players in cell cycle control, and genetic alterations of CDKs and their regulators have been linked to a variety of cancers. Hence, CDKs are obvious targets for therapeutic intervention in various proliferative diseases, including cancer. To date, drug design efforts have mostly focused on CDK2 because methods for crystallization of its inhibitor complexes have been well established. CDK4 and CDK6, however, may be at least as important as enzymes for cell cycle regulation and could provide alternative treatment options. We describe here two complex structures of human CDK6 with a very specific kinase inhibitor, PD0332991, which is based on a pyrido[2,3-d]pyrimidin-7-one scaffold, and with the less specific aminopurvalanol inhibitor. Analysis of the structures suggests that relatively small conformational differences between CDK2 and CDK6 in the hinge region are contributing to the inhibitor specificity by inducing changes in the inhibitor orientation that lead to sterical clashes in CDK2 but not CDK6. These complex structures provide valuable insights for the future development of CDK-specific inhibitors.
<StructureSection load='2f2c' size='340' side='right'caption='[[2f2c]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2f2c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Herpesvirus_saimiri_(strain_11) Herpesvirus saimiri (strain 11)] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F2C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F2C FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AP9:(2S)-2-({6-[(3-AMINO-5-CHLOROPHENYL)AMINO]-9-ISOPROPYL-9H-PURIN-2-YL}AMINO)-3-METHYLBUTAN-1-OL'>AP9</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2f2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f2c OCA], [https://pdbe.org/2f2c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f2c RCSB], [https://www.ebi.ac.uk/pdbsum/2f2c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f2c ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CGH2_SHV21 CGH2_SHV21] May be highly relevant to the process of cellular transformation and rapid T-cell proliferation effected by HVS during latent infections of T-cells in susceptible hosts.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f2/2f2c_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2f2c ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
2F2C is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Saimiriine_herpesvirus_2 Saimiriine herpesvirus 2] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=AP9:'>AP9</scene> and <scene name='pdbligand=DMS:'>DMS</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F2C OCA].
*[[Cyclin 3D structures|Cyclin 3D structures]]
 
*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
==Reference==
__TOC__
Toward understanding the structural basis of cyclin-dependent kinase 6 specific inhibition., Lu H, Schulze-Gahmen U, J Med Chem. 2006 Jun 29;49(13):3826-31. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16789739 16789739]
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Large Structures]]
[[Category: Protein complex]]
[[Category: Lu H]]
[[Category: Saimiriine herpesvirus 2]]
[[Category: Schulze-Gahmen U]]
[[Category: Lu, H.]]
[[Category: Schulze-Gahmen, U]]
[[Category: AP9]]
[[Category: DMS]]
[[Category: SO4]]
[[Category: small molecule inhibitor bound between n-terminal and c-terminal domain of kinase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:16:59 2008''

Latest revision as of 12:21, 14 February 2024

X-ray structure of human CDK6-Vcyclinwith the inhibitor aminopurvalanolX-ray structure of human CDK6-Vcyclinwith the inhibitor aminopurvalanol

Structural highlights

2f2c is a 2 chain structure with sequence from Herpesvirus saimiri (strain 11) and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.8Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CGH2_SHV21 May be highly relevant to the process of cellular transformation and rapid T-cell proliferation effected by HVS during latent infections of T-cells in susceptible hosts.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

2f2c, resolution 2.80Å

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